Treatment of autoimmune diseases such as rheumatoid arthritis and the like has been carried out by symptomatic therapy in which inflammation is relieved by a non-steroidal antiinflammatory drug (NSAID). The NSAID's are classified into acidic antiinflammatory drugs and basic antiinflammatory drugs.
On the other hand, recently, more attention has been paid to causal therapy in which immunopathy is improved by immunomodulatory activity. Examples of drugs used for causal therapy include D-penicillamine, levamisole, lobenzarit and the like.
Most of these NSAID's are acidic antiinflammatory drugs represented by aspirin, indomethacin and the like. They have disadvantage of causing serious side effects such as a stomach ulcer and there are difficulties in using them continuously for a long period for time. Further, although basic antiinflammatory drugs have strong analgesic activity they have weak antiinflammatory action and therefore they are unsuitable for chronic diseases.
Furthermore, immunomodulators are insufficient in their pharmacological effects, side effects, toxicity and the like. Thus, it is desired to develop better drugs which are suitable for both symptomatic and causal therapy.
Recently, adhesion protein [e.g., intercellular adhesion molecule (ICAM)] inhibitors which inhibit infiltration of inflammatory cells or block attachment of immunocytes which participate in antigen or cell recognition have been noted [Masayuki Miyasaka, Jikken-Igaku, 9, 289 (1991); D. L. Thiele and P. E. Lipsky, Immunology Today, 10, 375 (1989)]. There are possibilities that these drugs inhibit or mitigate inflammation by a mechanism different from the conventional one. Therefore, such drugs are expected to be antiinflammatory drugs, antiallergic drugs or immunosuppressants of a new generation.